Researchers have a new tool to study how breast cancer develops in women whose genes give them a chance of contracting the disease 70%. In May Nature Genetics , the researchers report that they have inactivated or knocked out, the BRCA1 gene in the mouse exclusively in cells where breast cancer normally takes root.
previous efforts to knocking out one or both copies of the gene in all tissues of the mouse produced disappointing results. Women with BRCA1 Mutations are born with an inactive copy of BRCA1 gene, while the other gets turned off later. But animals with an inactivated copy has not obtained any tumors, and those with two copies inactivated early died before birth.
To knock out the gene only in mammary tissue, teams led by Chu-Xia Deng and Lothar Hennighausen at the National Institute of Diabetes and Digestive and Kidney Diseases designed a mutant mouse strain so molecular scissors that would cut the BRCA1 genetically marked gene - but only in cells in the lining of the milk ducts chest. Indeed, after cutting the BRCA1 gene in the mammary tissue, some of the resulting mice had developed breast cancer in at least one of their 10 mammary glands from 10 to 13 months of age.
The researchers also shed light on how BRCA1 tumors develop. They already have binding evidence of BRCA1 default to the loss of p53 , the gene well known tumor suppressor that is itself mutated in about 50% of all cancers familial breast. Mouse p53 gene, they found, is either completely silent or severely blurred in two-thirds of tumors in their BRCA1 KOs. The researchers also found that inactivating a gene copy p53 in the BRCA1 mutants accelerated tumor formation in animals and significantly increased the incidence of cancer in about 75%.
"such an animal model is invaluable to understand the role of BRCA1 in familial breast cancer," said Andrew Futreal Centre Duke Medical University in Durham, North Carolina, a BRCA1 co discoverer. Moreover, Futreal said, the new animals might be useful to evaluate new treatments or chemotherapy drugs that could delay or even block the appearance of breast tumors.
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